One problem that has troubled physicians during the modern medical age is how to accurately measure the oxygenation state of a patient's tissues without resorting to an invasive procedure. This is important during many medical procedures because the physician needs to know when to transfuse more blood into a patient. When the oxygenation state of a patient's tissues is low, the physician should transfuse more blood or other oxygen carriers to increase the oxygen transportation rate. At the present time, most physicians rely on pulmonary artery catheterization to directly measure the oxygenation state of their patient's mixed venous blood during surgery. The physician then infers how well the patient's tissue is oxygenated from the measured oxygen content of the blood.
A physician can infer the oxygen state of the patient's tissue by knowing the partial pressure of oxygen in the mixed venous blood (PvO.sub.2) because of the equilibrium that exists between the partial pressure of oxygen (PO.sub.2) in the venous blood and the tissue. As arterial blood passes through the tissues, a partial pressure gradient exists between the PO.sub.2 of the blood in the arteriole entering the tissue and the tissue itself. Due to this pressure gradient, oxygen is released from hemoglobin in the red blood cells and also from solution in the plasma; the released 02 then diffuses into the tissue. The PO.sub.2 of the blood issuing from the venous end of the capillary cylinder will be a close reflection of the PO.sub.2 at the distal (venous) end of the tissue through which the capillary passes.
Under normal conditions the blood PO.sub.2 is essentially the same as that of interstitial fluid in contact with the outside of the capillary. The degree of equilibration between blood and tissue may depend on the speed of passage of blood through the capillary bed. If the blood moves through the capillary bed too quickly, the O.sub.2 may not have time to diffuse into the tissues. It has also been argued that, under conditions of critical oxygen delivery caused by extreme anemia, there may not be time for equilibration of tissue and the partial pressure of oxygen in the blood. These situations may lead to higher than expected mixed venous PO.sub.2 (PvO.sub.2). Nevertheless, in the clinical situation, it is generally accepted that the most reliable single physiological indicator for monitoring the overall balance between oxygen supply and demand is mixed venous oxygen tension. As discussed above, one mechanism for determining the mixed venous oxygen tension is through insertion of a pulmonary artery catheter that is passed through the right atrium and the right ventricle of the heart before entering the pulmonary artery by passage through the pulmonary valve.
To fully assess whole body oxygen transport and delivery, one catheter is placed in the patient's pulmonary artery and another in the brachial or femoral artery. Blood samples are then drawn from each catheter to determine the pulmonary artery and arterial blood oxygen levels. The patient's cardiac output may be obtained using the pulmonary arterial catheter by utilizing thermodilution techniques. By injecting a known quantity of a sterile solution at a known temperature into the right atrium of the heart, and then measuring the resultant change in blood temperature at the pulmonary artery, a physician can determine the cardiac output of the patient. Devices such as the Swan-Ganz.RTM. thermodilution catheter (Baxter International, Santa Ana, Calif.) are used in such procedures, but they require invasive procedures. While these procedures have proven to be somewhat accurate, they are also quite invasive. Moreover, catheterization can lead to an increased risk of infection, pulmonary artery bleeding from pneumothorax and other complications.
Another method of determining the oxygenation level of a patient's tissue is to measure the level of circulating hemoglobin in the blood. P. Lundsgaard-Hansen, Infusionstherapie (1989) 16:167-175. If the hemoglobin level per deciliter of blood in the patient is high, the physician can infer that the patient has sufficient capacity to carry oxygen to the tissue. Unfortunately, measuring the hemoglobin level in a patient only yields a rough estimate of how well the patient's tissues are actually oxygenated. The patient's cardiac output is also an important factor in correlating hemoglobin levels with tissue oxygenation states. Cardiac output is defined as the volume of blood ejected by the left ventricle of the heart into the aorta per unit of time (ml/min) and can be measured with a thermodilution catheter. For example, if a patient has internal bleeding, the concentration of hemoglobin in the blood might be normal, but the total volume of blood will be low. In this situation the heart responds by decreasing the cardiac output to provide better circulation to the tissues. For this reason, simply measuring the amount of hemoglobin in the blood without measuring other parameters such as cardiac output is not always sufficient for estimating the actual oxygenation state of the patient. However, in spite of this a majority of physicians still rely on hemoglobin measurements to gauge whether the patient's oxygenation is stable during surgery because other methods are too invasive.
The Fick equation (Fick, A. Wurzburg, Physikalisch edizinische Gesellschaft Sitzungsbericht 16 (1870)) relates the arterial oxygen concentration, venous oxygen concentration and cardiac output to the total oxygen consumption of a patient and can be written as: EQU (CaO.sub.2 -CvO.sub.2).times.CO=VO.sub.2
where CaO.sub.2 is the arterial oxygen content, CvO.sub.2 is the venous oxygen content, CO is the cardiac output and VO.sub.2 represents whole body oxygen consumption.
The VO.sub.2 level can be calculated from the difference between inspired and mixed expired oxygen and the *minute volume of ventilation.
Others have attempted to non-invasively infer cardiac output by measuring arterial blood pressure instead of relying on thermodilution catheters. For example, Kraiden et al. (U.S. Pat. No. 5,183,051) use a blood pressure monitor to continuously measure arterial blood pressure data. These data are then converted into a pulse contour curve waveform. From this waveform, Kraiden et al. calculate the patient's cardiac output.
During hemodilution, either intentionally as part of an autologous blood conservation program, or following surgical bleeding with maintenance of normovolemia, the Hb concentration and arterial O.sub.2 content (CaO.sub.2) decrease. As the red cell concentration falls, a reduction in whole blood viscosity occurs. This factor, together with the simultaneous increase in venous blood return, causes a rise in cardiac output (CO). The rise in cardiac output results in improved O.sub.2 transport to the tissues (DO.sub.2). The degree to which this physiological compensation occurs primarily depends on the CO response to the reduction in red cell mass. Some authorities have concluded that the relationship between a decrease in Hb concentration and increase in CO is linear. (Fan et al, Am. J. Physiol. 1980; H545-H552; Robertie and Graylee, International Anesthesiology Clinics 1990 28(4) :197-204), whereas others have maintained that it follows a curvilinear relationship (Lundsgaard-Hansen, P., Vox. Sang. 1979, 36:321-336). However, the degree of curvature found was very minimal, leading many researchers to perform calculations that assume a linear relationship (Hint, H., Acta Anaesthesiologica Belgica 1968, 2:119-138).
In man, the extent to which cardiac output rises as Hb concentration decreases can vary between 0.25 liters per minute per gm of Hb change to 0.70 L/min/g. Hence, the cardiac output response to hemodilution differs between patients thereby effecting the Hb level at which additional oxygen carrying capacity in the blood is required. This is one reason that measuring Hb levels is not a good reflection of a patient's tissue oxygenation level. The necessity for red blood cell transfusions also varies depending on such factors as vascular tone, which will cause the viscosity contribution to total systemic resistance to vary, and the ability of the myocardium to function at low Hb levels.
During moderate hemodilution, myocardial blood flow increases proportionately more than total cardiac output and hence, in the absence of significant coronary atherosclerosis, no myocardial ischemia occurs. It has been shown, however, that low postoperative hematocrit (Hct) may be associated with postoperative ischemia in patients with generalized atherosclerosis. Though a number of researchers have attempted to define a critical Hct level most authorities would agree that an empiric automatic transfusion trigger should be avoided and that red cell transfusions should be tailored to the individual patient. The transfusion trigger, therefore, should be activated by the patients own response to anemia--indeed, for patients under anesthesia it is recommended that in the absence of risks, transfusion is not indicated, independent of hemoglobin level.
If PvO.sub.2 is accepted as a reasonable indicator of patient safety, the question arises to what can be considered a "safe" level of this parameter. Though much data exists on critical oxygen delivery levels in animals, there is little to indicate what a critical PvO.sub.2 might be in the clinical situation. The available data indicates that the level is extremely variable. For instance, in patients about to undergo cardiopulmonary bypass, critical PvO.sub.2 varied between about 30 mm Hg and 45 mm Hg (Shibutani et al, Crit. Care Med. 1983, 11(8): 640-643); the latter value is well within the range of values found in normal, fit patients. Furthermore, shunting of blood in the tissues will cause elevated levels of PvO.sub.2, such as is found in patients in septic shock, and will result in O.sub.2 supply dependency (Moshenifar et al, CHEST 1983, 84(3): 267-271).
A PvO.sub.2 value of 35 mm Hg or more may be considered to indicate that overall tissue oxygen supply is adequate, but this is implicit on the assumption of an intact and functioning vasomotor system. This PvO.sub.2 level is reached at a Hb of about 4 g/dL in patients with good cardiopulmonary function. Even lower PvO.sub.2 levels are tolerated in some patients when increased fractional inspired O.sub.2 concentrations (FiO.sub.2 s) are employed. During surgery it is necessary to maintain a wide margin of safety and probably best to pick a PvO.sub.2 transfusion trigger at which the patient is obviously in good condition as far as oxygen dynamics are concerned. In practice, only certain patients will be monitored with a pulmonary artery catheter; thus, PvO.sub.2 will not be available for all patients, leaving the majority to be monitored with the imperfect trigger of Hb concentration. Therefore, a need exists for a system to accurately assess, in real-time, the PvO.sub.2 of a patient.